Genomes and Genes
Gene Symbol: Ins2
Description: insulin II
Alias: AA986540, Ins-2, InsII, Mody, Mody4, insulin-2, proinsulin
Publications185 found, 100 shown here
- Ghrelin cells replace insulin-producing beta cells in two mouse models of pancreas developmentCatherine L Prado
Department of Pediatrics, Barbara Davis Center, University of Colorado Health Sciences Center, 4200 East 9th Avenue, Denver, CO 80262, USA
Proc Natl Acad Sci U S A 101:2924-9. 2004..2 and Pax4 are required to specify or maintain differentiation of the beta cell fate. This finding also suggests that there is a genetic component underlying the balance between insulin and ghrelin in regulating glucose metabolism...
- Insulin-promoter-factor 1 is required for pancreas development in miceJ Jonsson
Department of Microbiology, University of Umea, Sweden
Nature 371:606-9. 1994..These findings show that IPF1 is needed for the formation of the pancreas and suggest that it acts to determine the fate of common pancreatic precursor cells and/or to regulate their propagation...
- The forkhead transcription factor Foxo1 links insulin signaling to Pdx1 regulation of pancreatic beta cell growthTadahiro Kitamura
Naomi Berrie Diabetes Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York, USA
J Clin Invest 110:1839-47. 2002..We propose that insulin/IGFs regulate beta cell proliferation by relieving Foxo1 inhibition of Pdx1 expression in a subset of cells embedded within pancreatic ducts...
- Circulating sphingolipid biomarkers in models of type 1 diabetesTodd E Fox
Department of Pharmacology, Penn State College of Medicine, Milton S Hershey Medical Center, Hershey, PA, USA
J Lipid Res 52:509-17. 2011..metabolites by LC-MS/MS from two animal models of type 1 diabetes (streptozotocin-induced diabetic rats and Ins2(Akita) diabetic mice) to identify putative therapeutic targets and biomarkers...
- Islet-1 regulates Arx transcription during pancreatic islet alpha-cell developmentJingxuan Liu
Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
J Biol Chem 286:15352-60. 2011..Isl-1 represents the first known activator of Arx transcription in α-cells, here established to be acting through the conserved Re1 and Re2 control domains...
- SOX9 is required for maintenance of the pancreatic progenitor cell poolPhilip A Seymour
Department of Developmental and Cell Biology, University of California, Irvine, CA 92697 2300, USA
Proc Natl Acad Sci U S A 104:1865-70. 2007..These findings will be of major significance for the development of in vitro protocols for cell replacement therapies...
- Lack of both bradykinin B1 and B2 receptors enhances nephropathy, neuropathy, and bone mineral loss in Akita diabetic miceMasao Kakoki
Department of Pathology and Laboratory Medicine and Nutrition, University of North Carolina, Chapel Hill, NC 27599, USA
Proc Natl Acad Sci U S A 107:10190-5. 2010..nephropathy, neuropathy, and osteopathy in male mice heterozygous for the Akita diabetogenic mutation in the insulin 2 gene (Ins2)...
- Nkx6 transcription factors and Ptf1a function as antagonistic lineage determinants in multipotent pancreatic progenitorsAshleigh E Schaffer
Department of Pediatrics, University of California, San Diego, La Jolla, CA 92093, USA
Dev Cell 18:1022-9. 2010..Thus, cross-antagonism between Nkx6 and Ptf1a in multipotent progenitors governs the equilibrium between endocrine and acinar cell neogenesis required for normal pancreas development...
- Pancreas-specific deletion of beta-catenin reveals Wnt-dependent and Wnt-independent functions during developmentJessica Dessimoz
Swiss Institute for Experimental Cancer Research, Chemin des Boveresses 155, Case Postale, CH 1066 Epalinges s Lausanne, Switzerland
Curr Biol 15:1677-83. 2005..These effects are likely to be due to the function of beta-catenin at the membrane. Mice later recover from pancreatitis and regenerate normal pancreas and duodenal villi from the wild-type (wt) cells that escape beta-catenin deletion...
- Stabilization of beta-catenin impacts pancreas growthPatrick W Heiser
Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
Development 133:2023-32. 2006..Taken together, these data suggest a previously unappreciated temporal/spatial role for beta-catenin signaling in the regulation of pancreas organ growth...
- Tissue-specific remodeling of the mitochondrial proteome in type 1 diabetic akita miceHeiko Bugger
Division of Endocrinology, Metabolism and Diabetes, and Program in Molecular Medicine, University of Utah School of Medicine, Salt Lake City, Utah, USA
Diabetes 58:1986-97. 2009..To elucidate the molecular basis for mitochondrial dysfunction, which has been implicated in the pathogenesis of diabetes complications...
- Hyperglycemic Ins2AkitaLdlr⁻/⁻ mice show severely elevated lipid levels and increased atherosclerosis: a model of type 1 diabetic macrovascular diseaseChangcheng Zhou
Laboratory of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY, USA
J Lipid Res 52:1483-93. 2011..macrovascular disease, we have generated type 1 diabetic Akita mice lacking the low density lipoprotein receptor (Ins2(Akita)Ldlr⁻/⁻). Ins2(Akita)Ldlr⁻/⁻ mice were severely hyperglycemic with impaired glucose tolerance...
- Nkx2.2 and Arx genetically interact to regulate pancreatic endocrine cell development and endocrine hormone expressionTeresa L Mastracci
Department of Genetics and Development, Russ Berrie Medical Pavilion, Columbia University, 1150 St Nicholas Ave, New York, NY 10032, USA
Dev Biol 359:1-11. 2011..Together, these experiments identify novel genetic interactions between Nkx2.2 and Arx within the endocrine progenitor cells that ensure the correct specification and regulation of endocrine hormone-producing cells...
- Opposing actions of Arx and Pax4 in endocrine pancreas developmentPatrick Collombat
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, D 37077 Gottingen, Germany
Genes Dev 17:2591-603. 2003..We propose that the antagonistic functions of Arx and Pax4 for proper islet cell specification are related to the pancreatic levels of the respective transcripts...
- Beta-catenin is essential for pancreatic acinar but not islet developmentL Charles Murtaugh
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
Development 132:4663-74. 2005..Thus, our data are consistent with a crucial role for canonical Wnt signals in acinar lineage specification and differentiation...
- Ablation of the glucagon receptor gene increases fetal lethality and produces alterations in islet development and maturationPatricia M Vuguin
Division of Pediatric Endocrinology, Children s Hospital at Montefiore Medical Center, 111 East 210th Street, Bronx, New York 10476, USA
Endocrinology 147:3995-4006. 2006..These findings suggest that GLU participates in a feedback loop that regulates the proportion of the different endocrine cell types in islets, the number of islets per pancreas, and development of the mature alpha-cell phenotype...
- Regulation of renal fatty acid and cholesterol metabolism, inflammation, and fibrosis in Akita and OVE26 mice with type 1 diabetesGregory Proctor
Department of Medicine, Division of Renal Diseases and Hypertension, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Diabetes 55:2502-9. 2006....
- Dendrite remodeling and other abnormalities in the retinal ganglion cells of Ins2 Akita diabetic miceMatthew J Gastinger
Department of Ophthalmology, Penn State Retina Research Group, Penn State College of Medicine, Milton S Hershey Medical Center, Hershey, Pennsylvania 17033, USA
Invest Ophthalmol Vis Sci 49:2635-42. 2008To determine the extent of retinal ganglion cell loss and morphologic abnormalities in surviving ganglion cells in Ins2 Akita/+ diabetic mice.
- A dosage-dependent requirement for Sox9 in pancreatic endocrine cell formationPhilip A Seymour
Department of Developmental and Cell Biology, University of California, Irvine, Irvine, CA 92697 2300, USA
Dev Biol 323:19-30. 2008..Our findings therefore suggest that defective endocrine specification might underlie the pancreatic phenotype of individuals with CD...
- Maternal diabetes adversely affects preovulatory oocyte maturation, development, and granulosa cell apoptosisAimee S Chang
Department of Obstetrics and Gynecology, Division of Reproductive Endocrinology, Washington University in St Louis, St Louis, Missouri 63110 1094, USA
Endocrinology 146:2445-53. 2005..In addition, there may be dysfunctional or decreased communication in diabetic oocytes, as demonstrated by lower expression of connexin-43...
- The p48 DNA-binding subunit of transcription factor PTF1 is a new exocrine pancreas-specific basic helix-loop-helix proteinA Krapp
Swiss Institute for Experimental Cancer Research ISREC, Epalinges Lausanne, Switzerland
EMBO J 15:4317-29. 1996..Thus the pancreas-specific DNA-binding activity of PTF1 originates from the synthesis of at least one cell-specific component rather than from a cell-specific assembly of more widely distributed proteins...
- Expression of neurogenin3 reveals an islet cell precursor population in the pancreasV M Schwitzgebel
Hormone Research Institute, Department of Pediatrics, and Department of Medicine, University of California San Francisco, San Francisco, CA 94143, USA
Development 127:3533-42. 2000....
- Foxa2 is required for the differentiation of pancreatic alpha-cellsCatherine S Lee
Department of Genetics and Penn Diabetes Center, University of Pennsylvania School of Medicine, 415 Curie Boulevard, CRB 560 Philadelphia, PA 19104, USA
Dev Biol 278:484-95. 2005..By marker gene analysis, we show that the expression of the alpha-cell transcription factors Arx, Pax6, and Brn4 does not require Foxa2 in the transcriptional hierarchy governing alpha-cell differentiation...
- RNA-mediated gene duplication: the rat preproinsulin I gene is a functional retroposonM B Soares
Mol Cell Biol 5:2090-103. 1985....
- Complications of IgA nephropathy in a non-insulin-dependent diabetes model, the Akita mouseToshiyuki Haseyama
Department of Hygiene, Akita University School of Medicine, Akita 010 8543, Japan
Tohoku J Exp Med 198:233-44. 2002The Akita mouse, which has a mutation (Cys96Tyr) in the insulin 2 gene (Ins2(Akita)), is a model for diabetes. The male Akita mouse has diabetes, while females develop mild diabetes...
- Genetic identification of a novel NeuroD1 function in the early differentiation of islet alpha, PP and epsilon cellsCHRISTINA S CHAO
University of Colorado at Denver and Health Science Center, Biochemistry and Molecular Genetics Department, Aurora, CO 80045, USA
Dev Biol 312:523-32. 2007..Furthermore, this study reveals a previously unappreciated early function of NeuroD1 in regulating the specification of alpha, PP and epsilon cells...
- Islet-1 is required for the maturation, proliferation, and survival of the endocrine pancreasAiping Du
Department of Pathology and Laboratory Medicine, Children s Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
Diabetes 58:2059-69. 2009....
- Pancreatic neurogenin 3-expressing cells are unipotent islet precursorsRenaud Desgraz
Department of Genetic Medicine and Development, University of Geneva Medical School, 1 rue Michel Servet, 1211 Geneva 4, Switzerland
Development 136:3567-74. 2009..We propose a model whereby Ngn3(+) cells are monotypic (i.e. unipotent) precursors, and use this paradigm to refocus ideas on how cell number and type must be regulated in building complete islets of Langerhans...
- Rfx6 directs islet formation and insulin production in mice and humansStuart B Smith
Diabetes Center, University of California San Francisco, San Francisco, California 94143, USA
Nature 463:775-80. 2010..These studies demonstrate a unique position for Rfx6 in the hierarchy of factors that coordinate pancreatic islet development in both mice and humans. Rfx6 could prove useful in efforts to generate beta-cells for patients with diabetes...
- Pancreatic β-cell Raf-1 is required for glucose tolerance, insulin secretion, and insulin 2 transcriptionEmilyn U Alejandro
Laboratory of Molecular Signalling in Diabetes, Diabetes Research Group, Department of Cellular and Physiological Sciences, University of British Columbia, Vancouver, BC, Canada
FASEB J 25:3884-95. 2011..However, islet insulin protein and insulin 2 mRNA, but not insulin 1 mRNA, were dramatically reduced in Raf-1-knockout mice...
- Arx and Nkx2.2 compound deficiency redirects pancreatic alpha- and beta-cell differentiation to a somatostatin/ghrelin co-expressing cell lineageSimon Kordowich
Department of Molecular Cell Biology, Max Planck Institute for Biophysical Chemistry, Am Fassberg, Gottingen, Germany
BMC Dev Biol 11:52. 2011..2-deficient pancreata. Hence in order to precise the functional link between both factors we performed a comparative analysis of Nkx2.2/Arx single- and double-mutants but also of Pax6-deficient animals...
- Glucagon-like peptide 1 (1-37) converts intestinal epithelial cells into insulin-producing cellsAtsushi Suzuki
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Ibaraki 305 8575, Japan
Proc Natl Acad Sci U S A 100:5034-9. 2003..Our findings suggest that efficient induction of insulin production in intestinal epithelial cells by GLP-1-(1-37) could represent a new therapeutic approach to diabetes mellitus...
- Decreased L-type Ca2+ current in cardiac myocytes of type 1 diabetic Akita mice due to reduced phosphatidylinositol 3-kinase signalingZhongju Lu
Department of Physiology and Biophysics and the Institute of Molecular Cardiology, Stony Brook University, Stony Brook, New York 11794 8151, USA
Diabetes 56:2780-9. 2007..Because PI 3-kinases are key mediators of insulin action, we investigated whether LTCC function is affected in diabetic animals due to reduced PI 3-kinase signaling...
- Human recombinant ACE2 reduces the progression of diabetic nephropathyGavin Y Oudit
Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada
Diabetes 59:529-38. 2010..Inhibition of ACE2 function accelerates diabetic kidney injury, whereas renal ACE2 is downregulated in diabetic nephropathy. We examined the ability of human recombinant ACE2 (hrACE2) to slow the progression of diabetic kidney injury...
- PDX-1 is required for pancreatic outgrowth and differentiation of the rostral duodenumM F Offield
Department of Cell Biology, Vanderbilt University School of Medicine, Nashville, TN 37232 2175, USA
Development 122:983-95. 1996..These results offer additional insight into the role of pdx-1 in the determination and differentiation of the posterior foregut, particularly regarding the proliferation and differentiation of the pancreatic progenitors...
- Homeobox gene Nkx6.1 lies downstream of Nkx2.2 in the major pathway of beta-cell formation in the pancreasM Sander
Hormone Research Institute, University of California San Francisco, San Francisco, CA 94143 0534, USA
Development 127:5533-40. 2000..Together, these experiments reveal two independently controlled pathways for beta-cell differentiation, and place Nkx6.1 downstream of Nkx2.2 in the major pathway of beta-cell differentiation...
- MicroRNA expression is required for pancreatic islet cell genesis in the mouseFrancis C Lynn
Diabetes Center, Hormone Research Institute, University of California San Francisco, 513 Parnassus Ave, San Francisco, CA 94143 0534, USA
Diabetes 56:2938-45. 2007..We tested the hypothesis that microRNAs (miRNAs), which limit gene expression through posttranscriptional silencing, modulate the gene expression cascades involved in pancreas development...
- PERK EIF2AK3 control of pancreatic beta cell differentiation and proliferation is required for postnatal glucose homeostasisWei Zhang
Department of Biology, Pennsylvania State University, University Park, Pennsylvania 16802, USA
Cell Metab 4:491-7. 2006..exhibit severe defects in fetal/neonatal beta cell proliferation and differentiation, resulting in low beta cell mass, defects in proinsulin trafficking, and abrogation of insulin secretion that culminate in permanent neonatal diabetes.
- The Pax4 gene is essential for differentiation of insulin-producing beta cells in the mammalian pancreasB Sosa-Pineda
Max Planck Institute for Biophysical Chemistry, Gottingen, Germany
Nature 386:399-402. 1997..A default pathway would explain the elevated number of alpha cells in the absence of Pax4...
- Mapping of murine diabetogenic gene mody on chromosome 7 at D7Mit258 and its involvement in pancreatic islet and beta cell development during the perinatal periodT Kayo
Department of Hygiene, Akita University School of Medicine, Akita 010, Japan
J Clin Invest 101:2112-8. 1998Mutation of the murine maturity-onset diabetes mellitus of the young (Mody) locus induces diabetes, but the effects of its homozygosity on the pancreas remain unknown...
- A switch from MafB to MafA expression accompanies differentiation to pancreatic beta-cellsWataru Nishimura
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, Boston, MA 02215, USA
Dev Biol 293:526-39. 2006..Thus, this redundancy in the function and expression of the large-Maf factors may explain the normal islet morphology observed in the MafA knockout mice at birth...
- Ghrelin is a novel target of Pax4 in endocrine progenitors of the pancreas and duodenumQian Wang
Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, Tennessee, USA
Dev Dyn 237:51-61. 2008..Together, our data further support the notion that Pax4 activity is necessary to establish appropriate patterns of gene expression in endocrine progenitors of the digestive tract...
- Preferential reduction of beta cells derived from Pax6-MafB pathway in MafB deficient miceWataru Nishimura
Section of Islet Transplantation and Cell Biology, Joslin Diabetes Center, USA
Dev Biol 314:443-56. 2008..Thus, Pax6 acts upstream of MafB, which in turn may trigger the expression of insulin and regulate the PDX-1 and MafA expression required for beta-cell maturation...
- Rfx6 is an Ngn3-dependent winged helix transcription factor required for pancreatic islet cell developmentJosselin Soyer
Institute of Genetics and Molecular and Cell Biology IGBMC, INSERM U 964, CNRS UMR7104, University of Strasbourg, Illkirch, France
Development 137:203-12. 2010..By contrast, beta cells, whose number is only slightly reduced, were no longer clustered in a compact islet. These data unveil Rfx6 as a novel regulator of islet cell development...
- Recovery from diabetes in mice by beta cell regenerationTomer Nir
Department of Cellular Biochemistry and Human Genetics, Hebrew University Hadassah Medical School, Jerusalem, Israel
J Clin Invest 117:2553-61. 2007..These results suggest that regenerative therapy for type 1 diabetes may be achieved if autoimmunity is halted using regeneration-compatible drugs...
- Cell adhesion molecule 1 is a novel pancreatic-islet cell adhesion molecule that mediates nerve-islet cell interactionsYu Ichiro Koma
Division of Pathology, Kobe University Graduate School of Medicine, Kobe, Japan
Gastroenterology 134:1544-54. 2008..An immunohistochemical screen showed that CADM1 is expressed in pancreatic islets. Here, we determined the cell types expressing CADM1 and examined its role in nerve-islet cell interactions...
- Loss of bradykinin signaling does not accelerate the development of cardiac dysfunction in type 1 diabetic akita miceAdam R Wende
Program in Molecular Medicine and Division of Endocrinology, Metabolism, and Diabetes, University of Utah, School of Medicine, Salt Lake City, Utah 84112, USA
Endocrinology 151:3536-42. 2010..B1 and B2 receptors (B1RB2R(-/-)) in the context of the Akita model of insulin-deficient type 1 diabetes (Ins2(Akita/+))...
- Sigma receptor 1 modulates endoplasmic reticulum stress in retinal neuronsYonju Ha
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, GA 30912 2000, USA
Invest Ophthalmol Vis Sci 52:527-40. 2011..To investigate the mechanism of σ receptor 1 (σR1) neuroprotection in retinal neurons...
- Proinsulin maturation disorder is a contributor to the defect of subsequent conversion to insulin in β-cellsJie Wang
Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA
Biochem Biophys Res Commun 411:150-5. 2011..Recently, we have found proinsulin is an aggregation-prone molecule inherent with a low relative folding rate and maintains a homeostatic balance ..
- Comparison of murine embryonic pancreatic development in vitro and in vivoFengxia Ma
State Key Laboratory of Experimental Hematology, Institute of Hematology, Chinese Academy of Medical Sciences, Tianjin, China
Pancreas 40:1012-7. 2011..The purpose of the present study was to compare the development of murine embryonic pancreas in vitro and in vivo...
- Integrin α1/Akita double-knockout mice on a Balb/c background develop advanced features of human diabetic nephropathyLing Yu
Division of Nephrology, Department of Medicine, Vanderbilt University, Nashville, Tennessee 37232, USA
Kidney Int 81:1086-97. 2012..Thus, the integrin α1KOAkitaKO Balb/c mouse represents a promising model presenting with most features of human diabetic nephropathy...
- Pancreas-specific deletion of mouse Gata4 and Gata6 causes pancreatic agenesisShouhong Xuan
Department of Genetics and Development, Columbia University, New York, New York 10032, USA
J Clin Invest 122:3516-28. 2012....
- Expression pattern of IAPP and prohormone convertase 1/3 reveals a distinctive set of endocrine cells in the embryonic pancreasMaria E Wilson
UCSF Diabetes Center, Department of Medicine, University of California, San Francisco, San Francisco, CA 94143 0534, USA
Mech Dev 115:171-6. 2002..The early production of atypical peptide hormones by these cells suggests that they could play an important role locally or systemically in the development of the embryo...
- Differential expression and imprinting status of Ins1 and Ins2 genes in extraembryonic tissues of laboratory miceL Deltour
Departement Genetique, Developpement et Pathologie Moleculaire, Institut Cochin, INSERM U567, CNRS UMR 8104, Universite Rene Descartes, 75014 Paris, France
Gene Expr Patterns 5:297-300. 2004There are two functional insulin genes in the mouse genome. The Ins2 gene is imprinted and expressed monoallelically from the paternal allele in the yolk sac. In the present study we have re-examined the imprinting status of Ins1...
- Intravenous administration of proinsulin 1 or 2-expressing fiber-mutant recombinant adenovirus vector protects against the development of diabetes in NOD miceKatsumi Yamada
Department of Internal and Geriatric Medicine, Kobe University Graduate School of Medicine, Kobe, Japan
Ann N Y Acad Sci 1150:183-6. 2008..Pins1-RGD and that of Ad.Pins2-RGD. Our study suggests that systemic administration of fiber-mutant adenovirus vectors, which induce transient expression of proinsulin, may be applicable to a gene therapy inducing tolerance to insulin.
- Regulation of pancreas development by hedgehog signalingM Hebrok
Department of Molecular and Cellular Biology and Howard Hughes Medical Institute, Harvard University, Cambridge, MA 02138, USA
Development 127:4905-13. 2000..Defects in hedgehog signaling may lead to congenital pancreatic malformations and glucose intolerance...
- Targeted disruption of the Chop gene delays endoplasmic reticulum stress-mediated diabetesSeiichi Oyadomari
Department of Molecular Genetics, Kumamoto University School of Medicine, Kumamoto, Japan
J Clin Invest 109:525-32. 2002..The Akita mouse, which carries a conformation-altering missense mutation (Cys96Tyr) in Insulin 2, likewise exhibits hyperglycemia and a reduced beta cell mass...
- Neuronatin, a downstream target of BETA2/NeuroD1 in the pancreas, is involved in glucose-mediated insulin secretionKhoi Chu
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
Diabetes 54:1064-73. 2005..These results suggest for the first time an important role for NNAT in insulin secretion and for proper beta-cell function...
- MafB is required for islet beta cell maturationIsabella Artner
Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 723 Light Hall, Nashville, TN 37232, USA
Proc Natl Acad Sci U S A 104:3853-8. 2007..These results demonstrate that MafB plays a previously uncharacterized role by regulating transcription of key factors during development that are required for the production of mature alpha and beta cells...
- The morphogenesis of the pancreatic mesenchyme is uncoupled from that of the pancreatic epithelium in IPF1/PDX1-deficient miceU Ahlgren
Department of Microbiology, University of Umea, Sweden
Development 122:1409-16. 1996..Together these data provide evidence that PDX-1 acts cell autonomously and that the lack of a pancreas in the pdx1-/- mice is due to a defect in the pancreatic epithelium...
- Mice lacking the homeodomain transcription factor Nkx2.2 have diabetes due to arrested differentiation of pancreatic beta cellsL Sussel
Nina Ireland Laboratory of Developmental Neurobiology, Department of Psychiatry, University of California, San Francisco, CA 94143, USA
Development 125:2213-21. 1998..1. We propose that Nkx2.2 is required for the final differentiation of pancreatic beta cells, and in its absence, beta cells are trapped in an incompletely differentiated state...
- A mutation in the insulin 2 gene induces diabetes with severe pancreatic beta-cell dysfunction in the Mody mouseJ Wang
Department of Molecular Medicine, Gunma University, Maebashi, Japan
J Clin Invest 103:27-37. 1999..no gross defect in the transcription from the wild-type insulin 2 allele or two alleles of insulin 1, levels of proinsulin and insulin were profoundly diminished in the beta cells of Mody mice, suggesting that the number of wild-type (..
- Sequence and functional comparison in the Beckwith-Wiedemann region: implications for a novel imprinting centre and extended imprintingS Engemann
Max Planck Institut fur Molekulare Genetik, Ihnestrasse 73, D 14195 Berlin, Germany
Hum Mol Genet 9:2691-706. 2000..One of the genes outside the cluster, Obph1, is imprinted in mouse placenta indicating that at least in extra-embryonic tissues the imprinting cluster extends into a larger domain...
- Fgf10 is essential for maintaining the proliferative capacity of epithelial progenitor cells during early pancreatic organogenesisA Bhushan
INSERM 457, Hospital Robert Debre, 75019 Paris, France
Development 128:5109-17. 2001..These results indicate that Fgf10 signalling is required for the normal development of the pancreas and should prove useful in devising methods to expand pancreatic progenitor cells...
- ErbB signaling regulates lineage determination of developing pancreatic islet cells in embryonic organ cultureMari Anne Huotari
Biomedicum Helsinki, Program for Developmental and Reproductive Biology and Haartman Institute, University of Helsinki, Helsinki 00014, Finland
Endocrinology 143:4437-46. 2002..BTC, acting through EGF-R/erbB-1, is important for the differentiation of beta-cells. This could be applied in the targeted differentiation of stem cells into insulin-producing cells...
- Dominant negative pathogenesis by mutant proinsulin in the Akita diabetic mouseTetsuro Izumi
Department of Molecular Medicine, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi, Japan
Diabetes 52:409-16. 2003..Although the results of our previous study suggested that the mutant proinsulin 2 is misfolded and blocked in the transport from the endoplasmic reticulum to the Golgi apparatus, its dominant ..
- FGF10 signaling maintains the pancreatic progenitor cell state revealing a novel role of Notch in organ developmentGitte Anker Norgaard
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, CO 80262, USA
Dev Biol 264:323-38. 2003..These data suggest that FGF10 signaling serves to integrate cell growth and terminal differentiation at the level of Notch activation, revealing a novel second role of this key signaling system during pancreatic development...
- Dependence of self-tolerance on TRAF6-directed development of thymic stromaTaishin Akiyama
Division of Cellular and Molecular Biology, Institute of Medical Science, University of Tokyo, Shirokanedai, Minato ku, Tokyo 108 8639, Japan
Science 308:248-51. 2005..Engraftment of thymic stroma of TRAF6(-/-) embryos into athymic nude mice induced autoimmunity. Thus, TRAF6 directs the development of thymic stroma and represents a critical point of regulation for self-tolerance and autoimmunity...
- Prime role for an insulin epitope in the development of type 1 diabetes in NOD miceMaki Nakayama
Barbara Davis Center for Childhood Diabetes, University of Colorado Health Sciences Center, Denver, Colorado 80262, USA
Nature 435:220-3. 2005..Here we show that the proinsulin/insulin molecules have a sequence that is a primary target of the autoimmunity that causes diabetes of the non-..
- Attenuated Wnt signaling perturbs pancreatic growth but not pancreatic functionStella Papadopoulou
Umeå Centre for Molecular Medicine, University of Umea, S 901 87 Umea, Sweden
Diabetes 54:2844-51. 2005..Collectively, our data provide evidence that Wnt signaling is required for pancreatic growth but not adult beta-cell function...
- Notch/Rbp-j signaling prevents premature endocrine and ductal cell differentiation in the pancreasJunji Fujikura
Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara cho, Sakyo ku, Kyoto 606 8507, Japan
Cell Metab 3:59-65. 2006..Thus, our analyses indicate that Notch/Rbp-j signaling prevents premature differentiation of pancreatic progenitor cells into endocrine and ductal cells during early development of the pancreas...
- Conditional expression of Smad7 in pancreatic beta cells disrupts TGF-beta signaling and induces reversible diabetes mellitusNora G Smart
Department of Developmental Biology, Stanford University School of Medicine, Stanford, California, USA
PLoS Biol 4:e39. 2006..Thus, our studies reveal that TGF-beta signaling is crucial for establishing and maintaining defining features of mature pancreatic beta cells...
- MafB: an activator of the glucagon gene expressed in developing islet alpha- and beta-cellsIsabella Artner
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA
Diabetes 55:297-304. 2006..These results indicate that MafB is not only important to islet alpha-cell function but may also be involved in regulating genes required in both endocrine alpha- and beta-cell differentiation...
- Senescence-associated phenotypes in Akita diabetic mice are enhanced by absence of bradykinin B2 receptorsMasao Kakoki
Department of Pathology and Laboratory Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina 27599 7525, USA
J Clin Invest 116:1302-9. 2006..in B2 receptor-null mice, clearly apparent in mice diabetic because of a dominant mutation (Akita) in the Ins2 gene, and most obvious in Akita diabetic plus B2 receptor-null mice...
- The fringe molecules induce endocrine differentiation in embryonic endoderm by activating cMyt1/cMyt3Yanwen Xu
Vanderbilt University, Department of Cell and Developmental Biology, Nashville, TN 37232, USA
Dev Biol 297:340-9. 2006..These results suggest that Mfng-mediated repression of Notch signaling could serve as a trigger for endocrine islet differentiation...
- ATF4-mediated induction of 4E-BP1 contributes to pancreatic beta cell survival under endoplasmic reticulum stressSuguru Yamaguchi
Division of Molecular Metabolism and Diabetes, Tohoku University Graduate School of Medicine, Sendai, Miyagi 980 8575, Japan
Cell Metab 7:269-76. 2008..Thus, 4E-BP1 induction contributes to the maintenance of beta cell homeostasis during ER stress and is a potential therapeutic target for diabetes...
- Prominin 1 marks intestinal stem cells that are susceptible to neoplastic transformationLiqin Zhu
Department of Developmental Neurobiology, St Jude Children s Research Hospital, 262 Danny Thomas Place, Memphis, Tennessee 38105, USA
Nature 457:603-7. 2009..Our data indicate that Prom1 marks stem cells in the adult small intestine that are susceptible to transformation into tumours retaining a fraction of mutant Prom1(+) tumour cells...
- Role of SREBP-1 in the development of parasympathetic dysfunction in the hearts of type 1 diabetic Akita miceHo Jin Park
Tufts Medical Center, Molecular Cardiology Research Institute, 750 Washington St, Box 8486, Boston, MA 02111, USA
Circ Res 105:287-94. 2009..Sterol regulatory element binding protein-1 (SREBP-1) is a lipid-sensitive transcription factor...
- Developmental biology of the pancreasJ M Slack
Department of Zoology, Oxford University, UK
Development 121:1569-80. 1995....
- IPF1, a homeodomain-containing transactivator of the insulin geneH Ohlsson
Department of Microbiology, University of Umea, Sweden
EMBO J 12:4251-9. 1993..The pattern of IPF1 expression and its ability to stimulate insulin gene transcription suggest that IPF1 functions both in the regionalization of the primitive gut endoderm and in the maturation of the pancreatic beta-cell...
- Lineage-specific morphogenesis in the developing pancreas: role of mesenchymal factorsG K Gittes
Department of Surgery, University of California, San Francisco, USA
Development 122:439-47. 1996..In addition, the islets seem to form from early embryonic epithelium (which only express non-acinar genes). This formation occurs without any specific embryonic signals, and without any clear duct or acinus formation...
- Cadherins regulate aggregation of pancreatic beta-cells in vivoU Dahl
Department of Microbiology, University of Umea, Sweden
Development 122:2895-902. 1996..Thus, we have for the first time shown in vivo that cadherins regulate adhesive properties of beta-cells which are essential for the aggregation of endocrine cells into islets...
- A novel locus, Mody4, distal to D7Mit189 on chromosome 7 determines early-onset NIDDM in nonobese C57BL/6 (Akita) mutant miceM Yoshioka
Department of Hygiene, Akita University School of Medicine, Japan
Diabetes 46:887-94. 1997..This locus, which we named Mody4, was mapped to chromosome 7 in a region 2-8 cM distal to D7Mit189 (logarithm of odds [LOD] score = 15.6 and 10.3).
- Phenotypic alterations in insulin-deficient mutant miceB Duvillie
Institut Cochin de Genetique Moleculaire, Institut National de la Santé et de la Recherche Médicale U257, 24 rue du Faubourg Saint Jacques, 75014 Paris, France
Proc Natl Acad Sci U S A 94:5137-40. 1997Two mouse insulin genes, Ins1 and Ins2, were disrupted and lacZ was inserted at the Ins2 locus by gene targeting. Double nullizygous insulin-deficient pups were growth-retarded...
- Sonic hedgehog directs specialised mesoderm differentiation in the intestine and pancreasA Apelqvist
Department of Microbiology, University of Umea, Sweden
Curr Biol 7:801-4. 1997..These results provide evidence that the differential expression of endodermally derived Shh controls the fate of adjacent mesoderm at different regions of the gut tube...
- The bHLH protein PTF1-p48 is essential for the formation of the exocrine and the correct spatial organization of the endocrine pancreasA Krapp
Swiss Institute for Experimental Cancer Research, CH 1066 Epalinges, Switzerland
Genes Dev 12:3752-63. 1998....
- Molecular mechanisms and regulation of insulin exocytosis as a paradigm of endocrine secretionJ Lang
Division de Biochimie Clinque, Departement de Medecine Interne, Médical Universitaire, Geneve, Switzerland
Eur J Biochem 259:3-17. 1999..Insights into the progression of the exocytotic vesicle from docking to fusion and how these processes are precisely regulated by proteins and second messengers may provide the basis for new therapeutic principles...
- Pancreas dorsal lobe agenesis and abnormal islets of Langerhans in Hlxb9-deficient miceK A Harrison
Laboratory of Immunoregulation National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA
Nat Genet 23:71-5. 1999..Hlxb9-/- beta-cells express low levels of the glucose transporter Glut2 and homeodomain factor Nkx 6-1. Thus, Hlxb9 is key to normal pancreas development and function...
- Sequence-ready 1-Mb YAC, BAC and cosmid contigs covering the distal imprinted region of mouse chromosome 7R Kato
Department of Integrated Genetics, National Institute of Genetics and Graduate University for Advanced Studies, Mishima, Shizuoka, Japan
DNA Res 6:401-5. 1999....
- Sequence and comparative analysis of the mouse 1-megabase region orthologous to the human 11p15 imprinted domainP Onyango
Institute of Genetic Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
Genome Res 10:1697-710. 2000..This study provides the first global view of the architecture of an entire imprinted domain and provides candidate sequence elements for subsequent functional analyses...
- Compensatory responses in mice carrying a null mutation for Ins1 or Ins2L Leroux
Department of Genetics, Development and Molecular Pathology, ICGM, Institut National de la Santé et de la Recherche Médicale Unit 257, Paris, France
Diabetes 50:S150-3. 2001..and postnatal acute diabetes result from insulin deficiency in double homozygous null mutants for Ins1 and Ins2 (Duvillié B, et al., Proc. Natl. Acad. Sci. USA 94:5137-5140, 1997)...
- New mouse model to study islet transplantation in insulin-dependent diabetes mellitusClayton E Mathews
The Jackson Laboratory, Bar Harbor, ME 04609, USA
Transplantation 73:1333-6. 2002..This report examines the insulin sensitivity of mice that carry Ins2Akita and their responsiveness to engraftment with syngeneic pancreatic islets...
- Acceleration of type 1 diabetes mellitus in proinsulin 2-deficient NOD miceKarine Thébault-Baumont
Institut National de la Santé et de la Recherche Médicale INSERM U561, Hopital Cochin Saint Vincent de Paul, Paris, France
J Clin Invest 111:851-7. 2003Accumulating evidence favors a role for proinsulin as a key autoantigen in diabetes. In the mouse, two proinsulin isoforms coexist. Most studies point to proinsulin 2 as the major isoform recognized by T cells in the NOD mouse...
- The concerted activities of Pax4 and Nkx2.2 are essential to initiate pancreatic beta-cell differentiationJunfeng Wang
Department of Genetics and Tumor Cell Biology, St Jude Children s Research Hospital, Memphis, TN 38105, USA
Dev Biol 266:178-89. 2004..This role of Pax4 appears to be accomplished via its genetic interaction with another homeobox gene, Nkx2.2...
- Endothelial cell interactions initiate dorsal pancreas development by selectively inducing the transcription factor Ptf1aHideyuki Yoshitomi
Cell and Developmental Biology Program, Fox Chase Cancer Center, 7701 Burholme Avenue, Philadelphia, PA 19111, USA
Development 131:807-17. 2004..Additionally, we find that endothelial cells are necessary for the induction of both the insulin and glucagon genes...
- The endoplasmic reticulum stress response is stimulated through the continuous activation of transcription factors ATF6 and XBP1 in Ins2+/Akita pancreatic beta cellsJun ichi Nozaki
Department of Molecular and Cellular Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606 8397, Japan
Genes Cells 9:261-70. 2004The dominant C96Y mutation of one of the two murine insulin genes, Ins2, causes diabetes mellitus in 'Akita' mice. Here we established pancreatic islet beta cell lines from heterozygous mice (Ins2+/Akita)...
- Orpk mouse model of polycystic kidney disease reveals essential role of primary cilia in pancreatic tissue organizationDavid A Cano
Diabetes Center, Department of Medicine, University of California, San Francisco, CA 94143, USA
Development 131:3457-67. 2004..Thus, polaris and primary cilia function are required for the maturation and maintenance of proper tissue organization in the pancreas...
- GDF11 modulates NGN3+ islet progenitor cell number and promotes beta-cell differentiation in pancreas developmentErin B Harmon
Department of Developmental Biology, Stanford University, Stanford, CA 94305 5329, USA
Development 131:6163-74. 2004..Thus, our studies reveal mechanisms by which GDF11 regulates the production and maturation of islet progenitor cells in pancreas development...
- Longitudinal evaluation of memory performance and peripheral neuropathy in the Ins2C96Y Akita miceCosette Choeiri
School of Psychology, University of Ottawa, 11 Marie Curie, Room 215, Ottawa, Ont, Canada KIN 6N5
Behav Brain Res 157:31-8. 2005..We found that, up to the age of 34 weeks old, uncontrolled hyperglycemia produced peripheral neuropathy and reduced hippocampal GLUT3 levels in the absence of any effect on spatial memory processing...
- Matrix metalloproteinases 2 and 9 are dispensable for pancreatic islet formation and function in vivoSabina E Perez
Diabetes Center, Department of Medicine, University of California, San Francisco, California, 94143 0573, USA
Diabetes 54:694-701. 2005..However, islet formation is unaffected in transgenic mice with modified tissue inhibitor of metalloproteinase-1 (TIMP1) levels, suggesting that MMP activity may contribute little to islet morphogenesis in vivo...
- Myosin Va transports dense core secretory vesicles in pancreatic MIN6 beta-cellsAniko Varadi
Henry Wellcome Laboratories for Integrated Cell Signalling, School of Medical Sciences, University of Bristol, Bristol BS8 1TD, United Kingdom
Mol Biol Cell 16:2670-80. 2005..We conclude that MyoVa-driven movements of vesicles along the cortical actin network are essential for the terminal stages of regulated exocytosis in beta-cells...
- FLOW SHEAR INDUCED NF-KB MEDIATED REGULATIONSumathy Mohan; Fiscal Year: 2003..Understanding of NF- kappaB signaling mechanisms in VCAM-1 regulation can also be applied to other inflammatory conditions. ..
- Investigating the Molecular Mechanism of Hexose-induced Stress in Lens and RetinaPeter F Kador; Fiscal Year: 2010..Moreover, these studies should help identify new drug targets for the treatment of these diabetic complications. ..
- A Novel Tool to Understand Insulin Production and Failure in Pancreatic beta-CellIsrael Hodish; Fiscal Year: 2008..ER stress includes misfolding of proinsulin, the beta cell's major secretory protein product - the precursor in insulin biosynthesis...
- Multifunctional Antioxidants as Anti-Cataract AgentsPeter Kador; Fiscal Year: 2007..unreadable] [unreadable] [unreadable] [unreadable] [unreadable] [unreadable]..
- GLUCOKINASE GENE EXPRESSION IN PANCREATIC BETA CELLMark Magnuson; Fiscal Year: 2005..In Aim 2 we will establish true mouse models for PHHI and MODY-2 in order to correlate changes in enzyme kinetics with insuIin secretion and glucose homeostasis...
- Expression profiling of human isletsKLAUS KAESTNER; Fiscal Year: 2006....
- Nitric Oxide Defense Against Porphyromonas gingivalisRobert Gyurko; Fiscal Year: 2006..He is applying for the NIDCR Scholar Development and Faculty Transition Award to pursue scientific career as an independent investigator at Boston University School of Dental Medicine. [unreadable] [unreadable]..
- Nutrition, Early Development and Glucose MetabolismPatricia Vuguin; Fiscal Year: 2007..abstract_text> ..
- Development of C57BL/6 ES cell technology for high thoughput use.KLAUS KAESTNER; Fiscal Year: 2007..unreadable] [unreadable] [unreadable] [unreadable]..
- FUNCTIONAL GENOMICS OF THE BETA-CELLKLAUS KAESTNER; Fiscal Year: 2007..The new resources generated through this project will be made available to the NIDDK-funded biotechnology centers and the diabetes research community at large. ..
- A Molecular Marker for Cardiac Autonomic DysfunctionHo Jin Park; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Liver Biology, Development and DiseaseKLAUS KAESTNER; Fiscal Year: 2008..unreadable] [unreadable] [unreadable]..
- Foxm 1b endocrine pancreas growth and regenerationMaureen Gannon; Fiscal Year: 2009..A thorough understanding of Foxml regulation of 3 cell mass may lead to strategies for maintaining 3 cell mass and enhancing 3 cell proliferation in diabetics. ..
- In vivo study of diabetic hyperglycemia and inflammationRobert Gyurko; Fiscal Year: 2009..Moreover, findings on novel lipid inhibitors of inflammation will be important in evaluating the therapeutic potential of these compounds in resolving inflammation in periodontal and other inflammations. ..
- Mechanisms of endoderm specification along the A-P axis.James M Wells; Fiscal Year: 2010..Additionally, this information should allow us to coax embryonic stem cells into becoming important transplantable derivatives of endoderm, such as insulin-producing beta cells to treat patients with Type 1 diabetes. ..
- FUNCTION OF A GROWTH INDUCED GENE IN LIVER REGENERATIONKLAUS KAESTNER; Fiscal Year: 2003....
- HNF6 Function in the Pancreatic Endocrine LineageMaureen A Gannon; Fiscal Year: 2010..e. is HNF6 needed only at early stages of endocrine specification, or is it required continuously during embryogenesis for terminal differentiation and acquisition of mature function. ..